This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are 8 million individuals in the US with Chronic Kidney Disease (CKD), who suffer from marked functional impairment and an extraordinarily high risk of dementia and cognitive dysfunction. Although CKD is also associated with an increased rate of vascular disease, the role of brain ischemia in contributing to this cognitive impairment is unknown. In individuals without kidney disease, impaired cerebral blood flow (CBF) - as detected by nuclear medicine techniques - has been recently identified as a strong correlate of cognitive impairment and cognitive decline, and is associated with prevalent cardiovascular risk factors. However, the relationship between cerebral hypoperfusion and cognitive dysfunction has not been assessed in CKD. We are proposing to measure cerebral blood flow in a population of older adults (age>65) with moderate-advanced chronic kidney disease using single-photon emission computed tomography (SPECT). We will examine the association between renal function and cerebral hypoperfusion by comparing these measures with previously collected CBF data in age-similar hypertensives without kidney disease, through collaboration with Dr. Shari Waldstein of the Depts. of Psychology and Medicine. Additionally, we will combine these CBF measurements with brain MRI and cognitive function data to be collected in the CKD study population as part of an NIH-funded Research Career Development Award, and measures of physical function to be collected as part of a UMB Pepper Center Research Development Core Pilot Grant. We will examine the inter-relationship among cerebral perfusion, neurocognitive and physical function, and MRI-defined ischemic brain damage in CKD. These analyses are the first steps towards identifying opportunities to preserve brain function in individuals with CKD.